Upregulated Ca²⁺ Release from the Endoplasmic Reticulum Leads to Impaired Presynaptic Function in Familial Alzheimer's Disease.

ABSTRACT: Neurotransmitter release from presynaptic terminals is primarily regulated by rapid Ca²⁺ influx through membrane-resident voltage-gated Ca²⁺ channels (VGCCs). Moreover, accumulating evidence indicates that the endoplasmic reticulum (ER) is extensively present in axonal terminals of neurons and plays a modulatory role in synaptic transmission by regulating Ca²⁺ levels. Familial Alzheimer's disease (FAD) is marked by enhanced Ca²⁺ release from the ER and downregulation of Ca²⁺ buffering proteins. However, the precise consequence of impaired Ca²⁺ signaling within the vicinity of VGCCs (active zone (AZ)) on exocytosis is poorly understood. Here, we perform in silico experiments of intracellular Ca²⁺ signaling and exoc

SUBMITTER: Adeoye T 

PROVIDER: S-EPMC9315668 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature